{ "docId": "019dd923-622c-750b-8b9a-21918ac10c17", "docSlug": "f3db2294dcf9", "documentTitle": "Harmony Biosciences (HRMY)", "authorId": "58_Scorpion_Capital", "authorName": "Scorpion Capital", "documentKindSlug": "research-note", "documentKindLabel": "Research note", "sourceTypeSlug": "short_seller", "sourceTypeLabel": "Short seller", "presentationDate": "2023-03-28 00:00:00", "orientation": "landscape", "aspectRatio": 1.3333334, "pageNumber": 303, "pageCount": 366, "prevPage": 302, "nextPage": 304, "slideType": "expose_contradiction", "function": "expose_contradiction", "density": "dense", "nDataPoints": 0, "notes": "The slide uses a direct excerpt from a scientific paper to undermine a previous scientific claim.", "elementsJson": [ "paragraph", "screenshot" ], "metadataConfidence": 1, "imagePath": null, "slideHref": "/slides/019dd923-622c-750b-8b9a-21918ac10c17/303", "deckHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17", "deckJsonHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17.json", "deckAnchorHref": "/decks/019dd923-622c-750b-8b9a-21918ac10c17#slide-303", "components": [ { "bbox": { "h": 0.03, "w": 0.86, "x": 0.07, "y": 0.47 }, "kind": "callout", "text": "Conclusions from Bioprojet paper shows no association between histamine and narcolepsy/sleepiness", "attrs": null, "subkind": "primary", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "e761ddf5-fb92-4fd7-bfe8-2433a678208d", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "callout", "text": "The paper is striking in its honesty, which we attribute to Bioprojet already having terminated pitolisant by 2012, given its omission in Bioprojet papers around that time which mention other “lead compounds” for its H3 receptor program.", "attrs": null, "subkind": null, "toolName": "Visual emphasis", "toolSlug": "visual-emphasis", "confidence": null, "componentId": "019dd953-70f3-714d-84c7-3ec46e799ba2", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.42, "x": 0.51, "y": 0.51 }, "kind": "paragraph", "text": "To conclude, we report the results of the first use of a method that provides a highly sensitive and selective quantification of both CSF histamine and its metabolite t-MHA in a large population of patients affected with narcolepsy-cataplexy, other etiologies of non-hypocretin-1 deficient central hypersomnia, and neurological controls. Being without significant difference between groups. we believe. from a clinical point of view. that the measurement of CSF HA and t-MHA are not informative tools to differentiate etiologies of central hypersomnia or to assess the severity of centrally mediated hypersomnia. However,", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "33fc02cf-b454-4214-b5ea-24f210bb7810", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.43, "x": 0.07, "y": 0.51 }, "kind": "paragraph", "text": "Altogether, even if discrepancies exist between studies,5-8 CSF measurements of both HA and t-MHA appear non-informative biomarkers to diagnose and differentiate between etiologies of central hypersomnia with or without hypocretin deficiency. Our results may contrast with the positive clinical findings of the inverse agonist of the H3 receptor that enhance wakefulness in normal animals and decreases EDS in orexin-/- mice and human narcoleptic.25 However, our present results were in agreement to those reported between orexin-/- mice and WT mice showing normal cortical activity of HA neurons (assessed by measuring the cortical level of t-MHA) during the dark (active) period at baseline.25", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "3df2fc2c-c2e1-4c53-8d1e-18f3fbc46ada", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.35, "w": 0.86, "x": 0.07, "y": 0.07 }, "kind": "paragraph", "text": "The paper is striking in its honesty, which we attribute to Bioprojet already having terminated pitolisant by 2012, given its omission in Bioprojet papers around that time which mention other “lead compounds” for its H3 receptor program. The paper even reframes the original 2007 rodent paper, which is the primary evidence that pitolisant increases histamine levels in the brain, stating that it showed that there was no difference in histamine levels between control mice and orexin mice bred to have narcolepsy. We paste the concluding section of the study below: that histamine is a “non-informative biomarker...to diagnose...etiologies of central hypersomnia” and that “from a clinical point of view” histamine levels are “not informative tools to differentiate etiologies of central hypersomnia or to assess the severity of centrally mediated hypersomnia.”", "attrs": null, "subkind": "paragraph", "toolName": null, "toolSlug": null, "confidence": null, "componentId": "a7b058ec-8a77-4342-a2e7-a08bd8e87812", "frameworkName": null, "frameworkSlug": null }, { "bbox": null, "kind": "quote", "text": "“non-informative biomarker...to diagnose...etiologies of central hypersomnia” and that “from a clinical point of view” histamine levels are “not informative tools to differentiate etiologies of central hypersomnia or to assess the severity of centrally mediated hypersomnia.” — Bioprojet paper", "attrs": null, "subkind": null, "toolName": "Authority citation", "toolSlug": "authority-citation", "confidence": null, "componentId": "019dd953-70f3-714d-84c7-402e4c5118ee", "frameworkName": null, "frameworkSlug": null }, { "bbox": { "h": 0.02, "w": 0.4, "x": 0.07, "y": 0.95 }, "kind": "source-note", "text": "Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443762/pdf/aasm.35.10.1359.pdf", "attrs": null, "subkind": null, "toolName": null, "toolSlug": null, "confidence": null, "componentId": "bdecec46-3022-4433-bc82-e7824abe9e31", "frameworkName": null, "frameworkSlug": null } ], "metrics": [], "tools": [], "frameworks": [], "arcBeats": [], "loops": [], "imagePathAlt": null, "thumbSrc": null, "thumbSrcAlt": null, "locked": true }